From the Editor

The patient is depressed. The doctor has prescribed medications. But the patient doesn’t take them.

As a clinician, this scenario is too familiar with results that are too familiar – the patient doesn’t get better. What can we do to improve adherence?

In this week’s selection, we look at a new paper by Weil Cornell Medicine’s Jo Anne Sirey et al., considering this question. The authors do a randomized controlled trial with “a brief psychosocial intervention designed to improve adherence to pharmacotherapy for patients with depression.” So, is this intervention a game-changer? The authors find a five-fold increase in adherence during the first 6 weeks of care – but not much change in overall depressive symptoms.

153745515Pretty pill bottle: But how can we get patients to take the pills?

In this Reading, we review the paper.


Adherence and Depression

“Adherence to Depression Treatment in Primary Care: A Randomized Clinical Trial”

Jo Anne Sirey, Samprit Banerjee, Patricia Marino, Martha L. Bruce, Ashley Halkett, Molly Turnwald, Claire Chiang, Brian Liles, Amanda Artis, Fred Blow, Helen C. Kales

JAMA Psychiatry, 27 September 2017 Online First


Nonadherence to antidepressant therapy remains a major challenge to quality depression care. Rates of nonadherence among older adults range from 29% to 40% in the United States. Most depression management is provided in primary care, and higher rates of antidepressant nonadherence are documented in primary care compared with psychiatry sites. Although nonadherence is problematic throughout treatment, the first 6 weeks of treatment is a particularly critical period to promote adherence, with increased risks of treatment dropout, relapse, medication discontinuation, vulnerability to suicide, and greater economic burden among those who show early nonadherence to antidepressants. There is evidence that early adequate antidepressant dosing and good adherence are both associated with recovery from depression and may improve the long-term outcomes of patients with depression.

Key risk factors for nonadherence include age, comorbid conditions, beliefs about treatment, and concerns over adverse events. In the elderly population, additional risk factors may include patient variables such as the lack of a medication routine, retaining discontinued medications, combining prescriptions, and multiple storage locations. Medication adherence problems also increase with the total number of drugs prescribed. The average older American adult takes 3 prescription and 4 over-the-counter medications daily, and those with depression typically take more medications. Even in successful clinical intervention studies for older adults with depression, nonadherence is a challenge.

Although older adults face structural barriers (eg, costs of medications, distance from home to physician’s office), often negative attitudes are the most important factors affecting adherence. Perceived stigma predicts poorer medication adherence and treatment discontinuation among elderly people with depression. Older adults worry about having a diagnosis of depression, especially older adults of African descent. Low perceived symptom severity is associated with poorer adherence, and even when distress is acknowledged, many older adults feel they should not need mental health help. In a community-based study of older adults, when perceived costs outweighed perceived benefits, nonadherent behaviors were more likely.

The Treatment Initiation and Participation Program (TIP) is a brief psychosocial intervention designed to improve adherence to pharmacotherapy for patients with depression. The Treatment Initiation and Participation Program is informed by the theory of reasoned action and targets individual-level, modifiable factors such as psychological barriers (eg, stigma, self-efficacy), fears about antidepressants, misattributions about causes of depression, and the lack of an adherence strategy. The program helps patients address barriers, identify treatment benefits, and feel empowered to manage their medication regimen and communicate with the physician effectively.

For this 2-site randomized clinical effectiveness trial of TIP, we targeted the critical period of early adherence among middle-aged and older adults with a newly initiated antidepressant treatment for depression by their primary care physician (PCP). We hypothesized TIP participants would be more likely to be at least 80% adherent to their antidepressant medication at both 6 and 12 weeks after the prescription was provided compared with participants who received treatment as usual. In addition, we hypothesized that TIP participants would have a greater reduction of depressive symptoms compared with participants receiving treatment as usual. Finally, we explored whether greater adherence in the TIP and treatment as usual groups was associated with decreased depression at 24 weeks.

maxresdefaultJo Anne Sirey

So begins a paper by Sirey et al.

Here’s what they did:

  • Patients were randomized into two groups: a group monitored by their family doctor and a group who received TIP.
  • Inclusion criteria included patients who were 55 years and older; they had been prescribed an antidepressant for depression.
  • Exclusion criteria included active suicidality, current substance use, significant cognitive impairment, inability to communicate in English.
  • “The TIP intervention included 5 steps: (1) review symptoms and antidepressant regimen and conduct a barriers assessment; (2) define a personal goal that could be achieved with adherence; (3) provide education about depression and antidepressant therapy; (4) collaborate to address barriers to treatment participation; and (5) create an adherence strategy and empower the older adult to talk directly with the PCP about treatment.” There were three TIP sessions.
  • Different scales were used, including a Brief Medical Questionnaire (for medication compliance) at 6, 12, and 24 weeks.
  • Statistical analysis was done, including logical regression models.

Here’s what they found:

  • Of the 607 people identified, 231 agreed to participate, and were randomized (115 to the TIP group).
  • Demographically, participants tended to be older (treatment as usual: 67.8, TIP: 67.6), female (70.4%, 74.1%), and white (67.8%, 73.3%).
  • “Participants in the TIP group were 5 times more likely to be adherent to their antidepressant at week 6,” and “nearly 3 times more likely at week 12 after controlling for study site compared with participants in the treatment as usual group.”
  • “A combined measure of 80% adherence at 6 and 12 weeks showed that TIP participants as a group were 3 times more likely to be adherent at both 6 and 12 weeks combined.”
  • “The group rates of symptom improvement for the total sample did not differ significantly over time… However, TIP participants showed a significant improvement (24.9%) in depressive symptoms at 6 weeks… whereas treatment as usual participants showed a less robust, nonsignificant improvement…”

In this community-based effectiveness trial among adults 55 years and older who had been prescribed pharmacotherapy for depression in primary care, patients who participated in TIP were more likely to be adherent to their medication than participants who received treatment as usual. The 5-fold increase in adherence during the first 6 weeks of care supports the clinical usefulness of TIP to improve early adherence. Higher adherence among TIP participants was further sustained throughout the first 3 months of care. Although TIP did not significantly improve overall depression, the TIP group showed a significant early reduction in depressive symptoms.

A few thoughts:

  1. This is a good paper.
  1. This is also a very practical paper, dealing with a common and significant problem.
  1. The results are promising – there was a five-fold increase in adherence at six weeks. Nice.
  1. But it’s also true that people didn’t improve with regard to a reduction of symptoms. The authors themselves speak to this in the paper:

There was an early depression response among the TIP group, but both groups improved over time. There is emerging evidence of the differential impact of antidepressant medications on depression trajectory based on symptom clusters as well as the benefit of looking beyond symptom severity to predict treatment response. Targeted treatments and improved adherence could improve depression outcomes as adequate dosing remains a challenge for depression treatment especially in primary care, which continues to be the largest provider of mental health services for older adults. Recent research has documented that depression remains poorly managed in primary care, especially when compared with other chronic diseases.

  1. The first author, in an interview for another publication, commented:

We were disappointed that we didn’t see a wide-ranging effect on depression over the long haul. But the treatment that was offered was so diverse, including the type of medication, the dosing, and the adequacy of antidepressants, we should have understood earlier that that would affect our predictions of depression outcomes.

  1. At best then, we can see the TIP intervention as offering a partial win. But there remains a larger problem with the management of depression in patients treated in a primary care setting: the management itself.


Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.